Real-time cell toxicity profiling of Tox21 10K compounds reveals cytotoxicity dependent toxicity pathway linkage

PloS One
Jui-Hua HsiehScott S Auerbach

Abstract

Cytotoxicity is a commonly used in vitro endpoint for evaluating chemical toxicity. In support of the U.S. Tox21 screening program, the cytotoxicity of ~10K chemicals was interrogated at 0, 8, 16, 24, 32, & 40 hours of exposure in a concentration dependent fashion in two cell lines (HEK293, HepG2) using two multiplexed, real-time assay technologies. One technology measures the metabolic activity of cells (i.e., cell viability, glo) while the other evaluates cell membrane integrity (i.e., cell death, flor). Using glo technology, more actives and greater temporal variations were seen in HEK293 cells, while results for the flor technology were more similar across the two cell types. Chemicals were grouped into classes based on their cytotoxicity kinetics profiles and these classes were evaluated for their associations with activity in the Tox21 nuclear receptor and stress response pathway assays. Some pathways, such as the activation of H2AX, were associated with the fast-responding cytotoxicity classes, while others, such as activation of TP53, were associated with the slow-responding cytotoxicity classes. By clustering pathways based on their degree of association to the different cytotoxicity kinetics labels, we identified clus...Continue Reading

References

Feb 15, 2005·Biochemical and Biophysical Research Communications·Haruna KanekoMasahiko Miura
Sep 23, 2006·Nature Reviews. Cancer·Robert H Shoemaker
Jan 24, 2007·Physiological Reviews·Guido KroemerCatherine Brenner
Mar 13, 2008·Environmental Health Perspectives·Menghang XiaChristopher P Austin
Apr 14, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Matthew T MartinDavid J Dix
Sep 3, 2010·Journal of Nucleic Acids·Monika PodhoreckaPrzemyslaw Bozko
Mar 2, 2011·Nature Reviews. Drug Discovery·Oliver KeppGuido Kroemer
Apr 23, 2013·Environmental Health Perspectives·Raymond R TiceJohn R Bucher
May 21, 2013·Chemical Research in Toxicology·Daniel M RotroffRichard S Judson
Oct 19, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Lisa TruongRobert L Tanguay
Jun 25, 2014·Environmental Science & Technology·Daniel M RotroffRichard S Judson
Apr 24, 2015·Journal of Biomolecular Screening·Jui-Hua HsiehRaymond R Tice
Jun 13, 2015·Environmental Science & Technology·Patience BrowneRussell S Thomas
Aug 15, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Richard S JudsonRussell S Thomas
Sep 19, 2015·Assay and Drug Development Technologies·Sarah J DuellmanJolanta Vidugiriene
Oct 22, 2016·Current Research in Translational Medicine·Y LiuZ Wei
Aug 16, 2017·Environmental Science & Technology·Nisha S SipesStephen S Ferguson

❮ Previous
Next ❯

Citations

May 23, 2018·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·Shigeki MotoyamaMasayuki Mishima
Oct 20, 2020·PLoS Neglected Tropical Diseases·Helen WhitelandKarl F Hoffmann
Jan 13, 2021·Journal of Nanobiotechnology·Tae Hwan ShinGwang Lee
Feb 17, 2021·Cell Chemical Biology·Jayme L DahlinBridget K Wagner
Feb 16, 2019·Journal of Chemical Information and Modeling·Michael FernandezArtem Cherkasov
Jun 9, 2020·Ecotoxicology and Environmental Safety·Shengnan ZhangYuanhui Zhao

❮ Previous
Next ❯

Methods Mentioned

BETA
Assay
as

Software Mentioned

R package : trend

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.